Aim To construct a diabetic atherosclerosis mouse model and study the pathological characteristics of diabetic atherosclerosis.Methods Fifty 8-week-old male LDLR-/-mice were fed with standard diet for 2 weeks and then changed to high-fat diet,they were randomly divided into two groups.The diabetic atherosclerosis group was given intraperitoneal injection of low dose streptozotocin(STZ)for 5 days continuouly to establish the model,and the atheroscle-rosis group was given citrate buffer injection at the same time.The body mass,blood glucose and blood lipids of the mice in the two groups were detected for many times.At the age of 23 weeks,the mice were euthanized after glucose tolerance test.HE staining and oil red O staining were used to detect the gross and aortic root atherosclerosis,immunohistochemical staining was used to detect CD4,α-smooth muscle actin(α-SMA),EGF-like module-containing mucin-like hormone re-ceptor-like 1(EMR1),monocyte chemotactic protein-1(MCP-1),NOD-like receptor protein 3(NLRP3),vascular cell adhesion molecule-1(VCAM-1),matrix metalloproteinase-2(MMP-2)and tissue inhibitor of metalloproteinase-1(TIMP-1),Western blot was used to detect α-SMA,CD4,tumor necrosis factor-α(TNF-α),NLPR3,intercellular adhesion molecule-1(ICAM-1),and type Ⅰ and Ⅲ collagen.Results Compared with the atherosclerosis group,the body mass decreased,the levels of total cholesterol(TC),triglyceride(TG),low density lipoprotein cholesterol(LDLC)increased,and the levels of high density lipoprotein cholesterol(HDLC)decreased(P＜0.05)in the diabetic atherosclerosis group.Compared with the atherosclerosis group,the distribution of atherosclerotic plaques was diffuse and the area was increased in the diabetic atherosclerosis group,and the contents of lipids,T cells,macrophages,smooth muscle cells,type Ⅰ and Ⅲ colla-gen were increased(P＜0.05);the protein levels of TNF-α,MCP-1,MMP-2,NLRP3,ICAM-1 and VCAM-1 in vascular tissues were increased,while the content of TIMP-1 were decreased and MMP2/TIMP-1 were increased(P＜0.05).Conclusions LDLR-mouse model of diabetic atherosclerosis can be successfully established by STZ induction combined with high-fat diet,which can reflect the plaque composition and inflammatory characteristics of diabetes promoting atheroscle-rosis.It can be used as a relatively ideal pathological model for the study of diabetic macroangiopathy.

Objective:To explore the effect of physical activity trajectories on cognitive function in middle-aged and older adults.Methods:Based on data from the China Health and Retirement Longitudinal Study (CHARLS) from 2011 to 2020, 809 participants aged ≥45 were selected. General data, physical activity levels, and cognitive function were collected. The group-based trajectory model (GBTM) was used to establish the physical activity trajectory model, and multiple linear regression was applied to investigate factors affecting cognitive function in middle-aged and older adults and to analyze the relationship between physical activity trajectories and cognitive function.Results:The cognitive function score for the 809 middle-aged and older adults was (11.71±4.60), and the logarithmic metabolic equivalent of physical activity was (8.38±1.06). Based on GBTM, four physical activity trajectories were identified: stable group, slow-increase group, rapid-decrease group, and stable-decrease group. Multiple linear regression analysis showed that the stable and slow-increase activity trajectories, gender, age, marital status, and retirement status were significant factors influencing cognitive function in middle-aged and older adults ( P<0.01) . Conclusions:Physical activity trajectories are associated with cognitive function in middle-aged and older adults. Maintaining stable or slowly increasing physical activity is beneficial for cognitive health. Nurses should design targeted interventions based on factors influencing cognitive function.

Objective:To analyze the differential expression of breast milk-derived extracellular vesicles (BM-EV) from mothers of preterm and term infants .Methods:Breast milk samples were collected from preterm and term delivery (three cases in each) at the Women's Hospital of Nanjing Medical University in 2019. BM-EV was extracted using ultracentrifugation. After preliminary identification of the characteristics of BM-EV, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used for protein quantification. Significantly up-regulated differential proteins (fold change≥1.5 and P<0.05) in the preterm group were screened. GO and KEGG were performed to predict the differentially expressed proteins' functional annotation and determine associated signaling pathways. Mann-Whitney U test and Fisher's exact test were used for intergroup comparisons. Pearson's correlation test describes the correlation of protein quantification values between samples. The differences in protein abundance were compared between the two groups using a t-test, followed by multiple corrections. Additionally, significantly enriched GO terms and KEGG pathways of the differentially expressed proteins were screened based on the hypergeometric distribution. Results:(1) There were three primiparae in the preterm group and one in the term group. Marker proteins CD9, CD81, and HSP70 were enriched in the BM-EV of both groups. (2) Six samples were comparable between groups and showed high reproducibility within groups. The correlation of protein quantification values between samples was up to 0.99. Furthermore, the coefficient of variation was 11.21% for preterm samples and 19.72% for term, and the data values in the preterm group were relative. (3) A total of 945 proteins were identified, and 156 were differentially expressed between preterm and term BM-EV, with 83 significantly up-regulated in preterm BM-EV. In the up-regulated proteins, the top three high-abundance proteins were complemented C4a, fatty acid synthase, and sclerostin domain-containing protein-1. (4) The biological processes or cellular components with the highest enrichment in GO functional prediction were mainly involved in hemoglobin and glycogen biosynthesis, immunological synapse formation, and phagocytosis mediated by the Fc γ receptor signaling pathway. The most relevant KEGG pathways were ribosome-related, complement and coagulation cascades, neutrophil extracellular trap formation, and Fc γ receptor-mediated phagocytosis.Conclusion:The significantly up-regulated differential proteins in BM-EV may play a protective role by regulating immunity, gastrointestinal function, and energy metabolism in preterm infants.

Objective:To understand the current situation of nurses in 52 hospitals in China on mastery of knowledge about skin injury in the elderly based on the background of mixed-mode homogenization training.Methods:Using the convenient sampling method, a total of 1 067 nurses from 52 hospitals in China were selected as the research objects in January 2021. A self-designed questionnaire on knowledge of skin injury in the elderly was used to investigate the nurses through the questionnaire star and univariate analysis was used to analyze the influencing factors. A total of 1 067 questionnaires were distributed and 1 067 valid questionnaires were recovered, and the effective recovery rate was 100%.Results:The knowledge scores of pressure injury, incontinence-associated dermatitis, skin tear and xerosis cutis among 1067 nurses were (95.66±7.37) , (95.65±9.15) , (91.37±15.45) and (87.67±15.91) , respectively. The results of univariate analysis showed that hospital grade was the influencing factor of nurses' knowledge score of pressure injury, skin tear and incontinence-associated dermatitis ( P<0.05) , educational background was the influencing factor of nurses' knowledge score of skin tear ( P<0.05) , professional title was the influencing factor of nurses' knowledge scores of pressure injury, incontinence-associated dermatitis and xerosis cutis ( P<0.05) . Conclusions:Hospitals at all levels need to strengthen the theoretical and practical knowledge training for nurses on skin xerosis and skin tear in the elderly, especially for nurses with primary titles and lower education in grassroots hospitals.

Lung transplantation is the only effective treatment of end-stage lung diseases. Nevertheless, shortage of donor lungs has become increasingly prominent worldwide. A large quantity of patients died while waiting for lung transplantation. Urgent lung transplantation is a prioritized allocation strategy for donor lung transplantation according to the urgency of diseases, aiming to shorten the waiting time for donor lungs and reduce the fatality of patients on the waiting list for lung transplantation. However, no consensus has been reached worldwide on the definition, criteria and application of the terminology of urgent lung transplantation. In addition, the survival and net benefits of lung transplant recipients based on this allocation system are still controversial. On the basis of previous clinical research on urgent lung transplantation, the definition criteria, risk factors, survival outcomes, limitations and optimization measures were explicitly elucidated in this article, aiming to provide theoretical reference for comprehensive evaluation of the feasibility of urgent lung transplantation and further optimizing the allocation system of donor lungs.

Lung transplantation has become the most effective treatment of end-stage lung diseases. Along with persistent optimization of lung transplantation technique and perioperative management, the short-term clinical efficacy after lung transplantation has been significantly improved, whereas the long-term clinical prognosis remains unoptimistic. Besides chronic lung allograft dysfunction, postoperative malignant tumors also threaten the long-term survival of the recipients. Common malignant tumors following lung transplantation include nonmelanoma skin cancer, posttransplant lymphoproliferative disease and lung cancer. After solid organ transplantation, a large majority of the recipients require lifelong immunosuppressive therapy. The intensity of immunosuppressive therapy for the lung transplant recipients is generally higher than other organ transplant recipients. Immunosuppression is the main factor which leads to the impairment of anti-tumor immune monitoring function and promotes the incidence and development of malignant tumors. In this article, the risk factors, prevention and treatment of the most common malignant tumors after lung transplantation were reviewed, aiming to provide reference for comprehensive diagnosis and treatment of malignant tumors following lung transplantation.

Objective To investigate the mechanism of white matter damage (WMD) and the neuroprotective effect of Xenon on neonates with WMD.Methods Three-day-old SD rat pups (n =96) were randomly divided into the blank control group (n =24),the WMD control group (n =24),the Xenon intervention group A (n =24) and the Xenon intervention group B (n =24) by random number method according to their birth time.WMD rat models were successfully established by giving intraperitoneal injection of lipopolysaccharide(LPS) 0.05 mg/kg combined with carotid artery ligation and hypoxia for 1 hour in the WMD control group and the Xenon intervention groups.In the control group,only 9 g/L saline (0.05 mg/kg) was injected intraperitoneally,while carotid artery ligation and hypoxia were not administered.Rats in Xenon intervention group A and group B were given inhalation of 500 mL/L Xenon for 3 hours at 0 and 2 hours respectively after establishment of the models.Six rats in each group were randomly selected and decapitated at 0,24,48 and 72 hours after the intervention.The brain white matter on the right was analyzed by using HE staining and myelin basic protein(MBP) immunofluorescence staining,and real-time quantitative polymerase chain reaction was used to detect the expressions level of CLIC4 mRNA.Results (1) Brain tissue pathology:compared with the blank control group,the brain white matter on the right of the WMD control group and the Xenon intervention group A and group B had loose and disordered structure,nuclear pyknosis and cytoplasm loosening.However,the lesions in both Xenon intervention group A and group B were significantly less than those in the WMD control group,and there was no significant difference between the Xenon intervention group A and group B.(2) MBP measurement:the number of MBP-positive cells in the brain white matter on the right of WMD control group was significantly lower than that in the blank control group,while compared with WMD control group,they were significantly higher in Xenon intervention group A and group B.(3) CLIC4 mRNA expression level:compared with blank control group,the expressions levels of CLIC4 mRNA at most time point were higher both in the WMD control group and the Xenon intervention group A and group B (all P ＜ 0.05),except the time point 24 h in the Xenon intervention group A.The expressions of CLIC4 mRNA in group A and group B were significantly decreased compared with those in the WMD control group (all P ＜ 0.05).However,there were no significant differences between Xenon intervention group A and group B (P ＞ 0.05).Conclusions The expressions of CLIC4 mRNA in brain tissues on neonatal rats with WMD significantly increased,indicating that the mitochondrial pathway could be one of the pathological processes of WMD.Early Xenon intervention may reduce neonatal WMD by reducing the expression of CLIC4 mRNA,which plays a neuroprotective role.

Objective To investigate the pathogenesis of white matter damage (WMD) and the effects of xenon intervention on the expression of EphB4 and EphrinB2 mRNA in the brain tissue of neonatal rats.Method Three-day-old SD rat pups (n =96) were randomly assigned into sham group (n =24),model group (n =24),xenon intervention group 1 (n =24) and xenon intervention group 2 (n =24).The WMD model was established by injected of lipopolysaccharide (LPS) 0.05 mg/kg combined with ligation of the right carotid artery for 1 h in the last three groups.Rats in xenon intervention group 1 inhaled 50％ xenon immediately for 3 h after modeling,while rats in xenon intervention group 2 inhaled 50％ xenon for 3 h at 2 h after modeling.After the completion of xenon intervention,6 rat pups in each groups were sacrificed at 0 h,24 h,48 h and 72 h.The pathologic examination of periventricular tissue was conducted with hematoxylin-eosin staining (HE) and the expression of EphB4 and EphrinB2 mRNA was assayed by real-time quantitative polymerase chain reaction (RT-PCR).Statistical analysis was then performed.Result (1)The structure of white matter in model group became loose,band net-like,with significant nucleus pyknosis.The pathological damages in xenon intervention group 1 and 2 were lighter at 24 h,48 h and 72 h than model group,with less karyopycnosis.(2) Compared with the sham group,the expressions of EphB4 and EphrinB2 mRNA at 0 h,24 h,48 h and 72 h were significantly higher in the model group and xenon intervention group 1 and 2 (P ＜ 0.05),except for the EphB4 mRNA in xenon intervention group 1 at 72 h (P ＞ 0.05).The expressions of EphB4 and EphrinB2 mRNA at each time point in xenon intervention group 1 and 2 were decreased significantly than the model group (P ＜ 0.05),except for the EphB4 mRNA in xenon intervention group 2 at 72 h (P ＞ 0.05).However,there was no statistically significant difference on EphB4 and EphrinB2 mRNA between two xenon intervention groups at each time point (P ＞ 0.05).Conclusion The expression of EphB4 and EphrinB2 mRNA are appreciably increased in brain tissue of neonatal rats with WMD,which indicates the reactive angiogenesis.The intervention with xenon may play a neuroprotective role through reducing the expressions of EphB4/EphrinB2 mRNA and angiogenesis,and early intervention may be better.

OBJECTIVE To investigate the effect of overexpession of 18 ku translocator protein (TSPO) on the hippocampal dentate gyrus. METHODS Lentiviral (LV) vectors containing TSPO or the lentiviral sequence were infused into the hippocampus bilateral dentate gyri (2 × 108 TU · mL-1,1 μL per side)of mice. Behavioral tests were carried out. The anxiolytic-like behavior of mice was examined by such means as the elevated plus maze test , the staircase test , light dark box test for 12, 14 and 16 d, two behavioral despair models, tail suspension test and the forced swimming test for 16 and 18 d,respec?tively. Western blotting and ELISA were used to evaluate the TSPO expression and the concentration of allopregnanolone in hippocampal tissue (3 mm in diameter around the injection site on both sides) at the end of tests. RESULTS The results of behavioral experiments showed that TSPO overexpression group deneloped anxiolytic and antidepression-like behavior. LV-TSPO significantly increased the retention time in the central area〔14 ± 4 vs (25 ± 12)s,P<0.05〕. LV-TSPO significantly increased the percentage of entry into open arms entries percentage and the percentage of time spent in open arms time without changing total entries and total time in the elevated plus-maze test〔(13±8)%vs (26±18)%, P<0.05;(6 ± 6)%vs (27 ± 6)%, P<0.05)〕. LV-TSPO significantly decreased the number of rearings without changing the number of steps in staircase test (21±7 vs 12±5,P<0.05). LV-TSPO increased entries into the light area and retention time in light-dark transition test〔(18 ± 8)% vs (26 ± 7)%, P<0.05;72 ± 36 vs (191 ± 90)s, P<0.05)〕but significantly decreased immobility time in the tail suspension test and forced swimming test〔94±33 vs (36±20)s, P<0.01;137±36 vs (90±37)s, P<0.05)〕, without excitatory or inhibitory actions on the central nervous system. At the same time, the level of TSPO expression in hippocampal tissues (3 mm in diameter around the injection site on both sides) was significantly increased, so did the concentration of allopregnanolone (P<0.05). CONCLUSION Overexpression of TSPO in the hippocamus dentate gyrus of mice can induce anxiolytic and antidepressant-like behavior, and the downstream allo?pregnanolone biosynthesis at least partially mediates the behavioral effects.

OBJECTIVE To investigate the protective effect of selective 18 ku translocator protein (TSPO) ligand YL-IPA08 on corticosterone(CORT)-induced apoptosis of BV-2 cells and its potential mecha?nisms. METHODS BV-2 Cells were pretreated with selective TSPO ligand YL-IPA08 1-100 nmol · L-1 and(or) TSPO antagonist PK11195 100 nmol · L-1 for 2 h,and then co-incubated with CORT for another 24 h. The apoptosis rate was measured by flow cytometry. CCK-8 kit was used to test BV-2 cell viability. The protein expression of TSPO was determined by Western blotting. The level of allopreg?nanolone was detected by ELISA kit. RESULTS In line with positive drug-AC-5216, the cell apoptosis rate decreased in YL-IPA08 1-100 nmol · L-1 and CORT co-treatment groups(P<0.01), which was antago?nized by PK11195 100 nmol · L-1 treatment(P<0.05). Cell viability increased in YL-IPA08 100 nmol · L-1and CORT co-treatment groups (P<0.01), which was blocked by PK11195 100 nmol·L-1 treatment(P<0.01). The expression of TSPO and the level of allopregnanolone(P<0.01) were enhanced by YL-IPA08 100 nmol · L-1 pretreatment followed by CORT treatment. The enhancement of allopregnanolone level was blocked by PK11195 100 nmol·L-1 treatment(P<0.05). CONCLUSION YL-IPA08 can protect BV-2 cells from CORT induced apoptosis. The protective effect of YL-IPA08 may be conferred by the increasing level of TSPO expression and allopregnanolone.